OPRM1 and cholestasis: Methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, offers a unique mechanism of action that selectively targets opioid-induced gastrointestinal dysmotility while preserving central analgesic effects [11,12]. Methylnaltrexone has been used for the management of cholestasis related to cholangitis due to its reported effect on helping relax the sphincter of Oddi. This distinctive pharmacological profile positions methylnaltrexone as a potential game-changer in the management of opioid-induced cholestasis that has the potential to proceed to acalculous cholecystitis [13,14].